# ROLE OF EICOSANOIDS IN HEMOPHILIC ARTHROPATHY

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 1990 · $204,204

## Abstract

Hemophiliacs develop recurrent joint bleeds, leading to chronic joint
symptomatology and disability. In the early stage of hemophilic arthropathy
neovascularization of the synovium occurs, which leads to a cycle of
rebleeding, greater degrees of proliferative changes, and siderosis.
Neovascularization appears to be a crucial phase of early hemophilic
arthropathy setting the stage for rebleeding and initiation of the chronic
joint disease that evolves. We hypothesize that in hemophilic arthropathy
synovial tissues and fluid produce increased amounts of proangiogenic and
decreased amounts of normally occurring antiangiogenic metabolites such
that abnormal synovial- neovascularization is favored. In preliminary work
(n-6) we have found that hemophilic synovial tissues and fluids produce
increased amounts of 15-HETE and LTB4, compounds we have shown to be
proangiogenic. In contrast the major hydroxyacid observed in control
(noninflammatory) arthritis is 12-HETE an eicosanoid we found to be
antiangiogenic. Other qualitative and quantitative differences in
eicosanoid product were also observed. Controls produced increased amounts
of prostaglandins (6KPGF1 alpha, PGD2, PGE2 and PGF2 alpha) when compared
to hemophilic joints. Qualitative differences in HETE production occurred.
Whereas hemophilic tissues produced LTB4, 15-HETE, 11-HETE, 5-HETE, 8,15
di-HETE, 5, 12 di-HETE, and HHT, controls produced 12-HETE as the major
product. We propose to expand these promising preliminary observations by a
systematic evaluation of eicosanoid production (prostaglandins, HETEs and
leukotrienes) in the synovial tissues and fluid of patients with hemophilic
arthropathy when compared to other control (non-inflammatory) arthritis. We
will ascertain the pro or antiangiogenic properties of these compounds in
various in vitro and in vivo angiogenic assays. The effects of these
eicosanoids on fibroblast and synovial cell proliferation will also be
assessed. Eicosanoid production in an animal model of hemophilic
arthropathy will be evaluated in relation to synovial neovascularization. A
final test of the pro or antiangiogenic properties of the compounds
identified will be the injection of these eicosanoids (singly or in
combinations) intraarticularly into control animal joints. The studies
proposed should elucidate the role of eicosanoids in hemophilic
arthropathy. The project could lead to the use of inhibitors of
cyclooxygenase, lipoxygenase, or leukotriene biosynthesis in an attempt to
modulate the animal (and ultimately) hemophilic-induced arthropathy.

## Key facts

- **NIH application ID:** 3158836
- **Project number:** 5R01AR038847-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **SAM.gov UEI:** QD4MGHFDJKU1
- **Principal Investigator:** MARIE J. STUART
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $204,204
- **Award type:** 5
- **Project period:** 1989-01-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158836

## Citation

> US National Institutes of Health, RePORTER application 3158836, ROLE OF EICOSANOIDS IN HEMOPHILIC ARTHROPATHY (5R01AR038847-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158836. Licensed CC0.

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